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US20040072366A1 - Method and device for manipulating small quantities of liquid - Google Patents

Method and device for manipulating small quantities of liquid Download PDF

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Publication number
US20040072366A1
US20040072366A1 US10/450,795 US45079503A US2004072366A1 US 20040072366 A1 US20040072366 A1 US 20040072366A1 US 45079503 A US45079503 A US 45079503A US 2004072366 A1 US2004072366 A1 US 2004072366A1
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United States
Prior art keywords
liquid
holding area
external force
area
generating
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US10/450,795
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Inventor
Achim Wixforth
Christoph Gauer
Jurgen Scriba
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Advalytix AG
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Advalytix AG
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Publication of US20040072366A1 publication Critical patent/US20040072366A1/en
Abandoned legal-status Critical Current

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0819—Microarrays; Biochips
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/089—Virtual walls for guiding liquids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0415—Moving fluids with specific forces or mechanical means specific forces electrical forces, e.g. electrokinetic
    • B01L2400/0427—Electrowetting
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0433—Moving fluids with specific forces or mechanical means specific forces vibrational forces
    • B01L2400/0439—Moving fluids with specific forces or mechanical means specific forces vibrational forces ultrasonic vibrations, vibrating piezo elements
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0442—Moving fluids with specific forces or mechanical means specific forces thermal energy, e.g. vaporisation, bubble jet
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0493—Specific techniques used
    • B01L2400/0496—Travelling waves, e.g. in combination with electrical or acoustic forces
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
    • Y10T436/00—Chemistry: analytical and immunological testing
    • Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
    • Y10T436/2575—Volumetric liquid transfer

Definitions

  • This invention relates to a device and method for manipulating small quantities of liquid on a solid body surface and a method for producing at least one defined quantity of liquid on a solid body surface.
  • liquid comprises inter alia pure liquids, mixtures, dispersions and suspensions, as well as liquids containing particles, e.g. biological material.
  • Such methods are used inter alia for inorganic reagents or organic material, such as cells, molecules, macromolecules or genetic materials, as described e.g. by O. Müller, Laborwelt 1/2000, pages 36 to 38.
  • the transport of small quantities of liquid in analysis and synthesis is undertaken in known methods in microstructured channels (Anne Y. Fu et al, Nature Biotechnology 17 , page 1109 ff. (1999)).
  • microstructured channels An already known technique is the transport of small quantities of liquid using micromechanical or electrostatic pumps in microstructured channels, as described in “Microsystem Technology in Chemistry and Life Sciences”, published by A. Manz and H. Becker (Springer Verlag, 1999), on pages 29 to 34.
  • Electrokinetic methods have been described by M. Köhler et al. (Physikalischet 56, Nr. 11, S. 57-61).
  • the object of the present invention is to provide an improved device and an improved method enabling effective manipulation of small quantities of liquid.
  • the device according to the present invention has at least one defined holding area on a solid body surface, on which the at least one liquid to be manipulated is preferably kept.
  • the at least one defined holding area has wetting properties other than the solid body surface surrounding it.
  • the defined holding area for the liquid can e.g. be in the form of “strip conductors” on the solid body surface, which can e.g. be realised by corresponding coating either of the defined holding area or its surroundings.
  • the wetting properties can be modulated e.g. by definition of hydrophilic or hydrophobic areas.
  • the preferred holding area is e.g. selected so that it is more hydrophilic than the surrounding solid body surface. This can be achieved either by hydrophilic coating of the preferred holding area or by hydrophobic surroundings.
  • a hydrophobic environment can e.g. be realised in a preferred design of the invention by a silanated surface.
  • the solid body surface surrounding the holding area can also be hydrophilic, lipophobic or lipophilic as compared to the surface of the holding area.
  • the preferred holding area is lipophilic compared to the surroundings.
  • the definition of the preferred holding area can also occur or be supported by etching the surface, whereby the etching depth is minimal relative to the width of the “strip conductor”, e.g. hundredth of the width.
  • the preferred holding area can be defined by the surface surrounding the preferred holding area being coated hydrophobically and being etched a few nanometres to a few micrometers into the surface in the vicinity of the holding area itself. In this way the contrast is increased with respect to the wetting angle. Yet macroscopically the surface is substantially planar. Such flat etching can be manufactured very easily and defined in manufacturing engineering terms, without the occurrence of known problems of deep etching of a narrow channel.
  • the wetting properties can also be modulated by microstructuring, as is the case with the so-called lotus effect, based on the varying, roughness of the surface. This can be obtained e.g. by microstructuring of the corresponding surface areas, e.g. by chemical treatment or ion radiation.
  • the at least one preferred holding area thus defined for the at least one quantity of liquid to be manipulated on the solid body surface has, according to the present invention, at least one constriction zone, whose width is less than the width of the adjacent parts of the preferred holding area.
  • the width is such that the quantity of liquid cannot overcome the constriction zone due to its surface tension without an external force being exerted.
  • the quantity of liquid for manipulating is on the preferred holding area of the solid body surface e.g. in the form of a droplet.
  • the surface of the liquid droplet exhibits the balanced same curvature everywhere, since a different curvature in different parts of the liquid droplet surface at any given surface tension would cause a different internal pressure.
  • Locally differing internal pressure in a droplet results, however, in a flow of liquid out of high-pressure areas into low-pressure areas. This occurs until there is pressure compensation, that is, the same curvature of surface is everywhere.
  • the wetting angle appears, which in balance and in an isotropic environment depends on both materials of the solid body surface or the liquid.
  • the curvature of the liquid surface is determined by the width of the preferred holding area, thus the “strip conductor”, and the volume of the quantity of liquid in this holding area. If the width of the “strip conductor” is altered abruptly, then the requirement for a constant curvature over the transition between both width does not have to be satisfied, since the height of the droplet, thus the “filling height”, would also be sharply altered here. Narrow “strip conductors” can therefore not be filled out easily by wide “strip conductors”, provided there is no external force being exerted.
  • the width of the “strip conductors” defined by the preferred holding areas for the transport of volumes of liquid in the region of picolitres is of the order of a few micrometers. For quantities of liquid of the order of nanolitres widths of 10 to several 100 micrometers are possible.
  • the width of the constriction zone essentially determines the strength of the external force required to overcome the constriction zone. The narrower the constriction zone, the greater the effect of the force has to be for a quantity of liquid to pass through the constriction zone. It has proven advantageous if the width of the constriction zones is less than half the width of the adjacent “strip conductors”. It is generally ensured that the surface tension prevents the constriction zone being overcome also without the effect of an external force.
  • the preferred holding area which is defined on the solid body surface, can be composed, in any form, of constriction zones and areas of greater width, thus “strip conductors” for the liquid.
  • a network or checker board of defined faces and delimiting constriction zones can be formed here, for example. With such a network small defined quantities of liquid can be propelled under the action of an external force from a partial area of defined surface via the interposed constriction zone into a second partial area of defined surface. In this way, a network of partial areas of defined surfaces can be filled selectively via interposed constriction zones. Small quantities of liquid can thus be positioned effectively inside a network.
  • the partial areas of the network between the constriction zones may be in various shapes.
  • a round shape is particularly advantageous, however.
  • the surface wetting properties at the edge of the face of the preferred holding area are defined very precisely and the quantity of liquid touches the edge of the partial area with defined face along its entire periphery with corresponding “filling ratio”.
  • the individual partial areas of defined surface can also have e.g. a functionalised surface, so that specific reactions can take place.
  • Other partial areas of defined surface can be used to perform chemical or physical analysis, e.g. by applying a local electrical or magnetic field, heating or e.g. a local mechanical force.
  • fluorescence analysis of a quantity of liquid on a specific partial area of defined surface can be performed by local detection. In other areas synthesis of different materials, which were brought in or as quantities of liquid onto a holding area of defined surface, can be carried out.
  • Areas having varying wetting properties or with differently functionalised surfaces can be manufactured simply and cost-effectively using already known lithographic processes and coating technologies.
  • thermodynamic parameters such as e.g. pressure and/or temperature.
  • volume of liquid which can be stored e.g. on a geometrically defined “standard volume”, is also determined by the thermodynamic parameters.
  • the thermodynamic parameters thus offer an option of varying the volume of liquid on at least a part of the preferred holding area in addition to the geometric dimensions in a specific area.
  • a particularly simple method is to increase the temperature, e.g. with a heating unit on the solid body surface.
  • This heating unit can either have a local effect on a holding area of defined surface or heat the entire solid body surface.
  • resistance heating is provided on the solid body surface. This generally causes the volume of liquid to expand and its surface tension drops. The result is thus a force which is capable of propelling the liquid across the constriction zone.
  • a micromechanical or a piezoelectrically driven pump is employed.
  • an electrode can be used on the solid body surface to move liquids with charged particles by electrostatic forces.
  • the device according to the present invention has at least one surface wave generation device.
  • This surface wave generation device generates surface waves which transfer an impulse to the quantities of liquid to be manipulated in the preferred holding area.
  • the impulse transmission is achieved either by mechanical deformation of the solid body surface or by the dynamic effect of the accompanying electrical fields on charged or polarisable material.
  • Surface waves can be generated on piezoelectric substrates or substrates with piezoelectric areas, e.g. piezoelectric coatings. It is adequate if the substrate or the corresponding coating is present only in the area where the surface wave generation device is located. The surface sound wave spreads out outside the piezoelectric area.
  • An interdigital transducer known per se is advantageously utilised to generate the surface wave.
  • Such an interdigital transducer has two electrodes which engage in one another like fingers.
  • a high-frequency alternating field e.g. of the order of several 100 MHz
  • a surface wave is stimulated, whose wave length results as quotient from the surface acoustic velocity and frequency, in a piezoelectric substrate or in a piezoelectric area of the substrate.
  • the direction of dispersion is perpendicular to the engaging finger electrode structures.
  • a well defined surface wave can be generated very easily by means of this type of interdigital transducer. Manufacturing the interdigital transducer is cost-effective and straightforward using known lithographic processes and coating technologies.
  • Interdigital transducers can also be controlled wireless, e.g. by irradiating an alternating electromagnetic field into an antenna device connected to the interdigital transducer.
  • a surface wave generation device whose surface wave expansion device is along the constriction zone, is provided for each constriction zone for this purpose. In this way at least part of a small quantity of liquid can be propelled from one part of the preferred holding area via the constriction zone into a second part of the preferred holding area with a defined surface via impulse transmission.
  • This surface defines a “standard volume” of a small quantity of liquid, which can be effectively filled or emptied. This happens at a defined point in time when the surface wave generation device is active.
  • a second surface wave Using the same or a second surface wave generation device, whose direction of dispersion is e.g. parallel to the direction of dispersion of the first surface wave generation device, a second surface wave, optionally with less intensity, can be sent in the direction of a volume of liquid in a part of the preferred holding area. Quantity and volume of the liquid can be ascertained through measuring of the attenuation of this second surface wave.
  • One arrangement of the network is particularly easy and secure to operate, wherein the constriction zones are vertical to one another and the directions of beam of at least two surface wave generation devices for filling or emptying the holding areas of defined surface are parallel to the constriction zones.
  • This arrangement is particularly secure, because there are essentially no impulse components which are common to the surface waves generated by the first or second surface wave generation device.
  • the surface wave generation device is designed as a so-called “tapered” interdigital transducer.
  • the finger distance along the axis of the transducer is not constant. The finger distance determines the wave length of the surface wave.
  • the device and method can also be used to create a defined volume of liquid.
  • the method according to the present invention can further be used to supply the quantities of liquid to be manipulated e.g. to an area on the solid body substrate, where analysis or synthesis is performed.
  • analysis or synthesis can e.g. be of a chemical, physical and/or biological nature.
  • a quantity of liquid can likewise be introduced to an area, where it reacts with another quantity of liquid.
  • the inventive device and method are suited both to analysis and to synthesis of the quantity of liquid or quantities of liquid.
  • the devices for generating an external force can be attached to electronic controls programmable via corresponding software.
  • FIG. 1 a is a diagrammatic plan view of an inventive embodiment for defining the smallest quantities of liquid
  • FIG. 1 b is a diagrammatic side elevation of the embodiment of FIG. 1 a .
  • FIG. 2 is a diagrammatic plan view of a second embodiment.
  • FIG. 1 partial areas 1 and 3 of a preferred holding area with a width, designated by 2 , are provided for the liquid to be manipulated.
  • the exact form of areas 1 and 3 and their width may be different.
  • Connecting to areas 1 and 3 are constriction zones 7 and 9 , which are created in the same way as areas 1 and 3 , as described further hereinbelow.
  • the constriction zones connect to a round area 5 .
  • the width 8 of the constriction zones 7 and 9 is less than half the width 2 of the areas 1 and 3 and must not necessarily be equal for different constriction zones.
  • the whole arrangement is situated on the surface of a solid body, e.g. a chip.
  • This can comprise e.g. piezoelectric material, e.g. quartz or LiNbO 3 , or have an at least partial piezoelectric surface, e.g. made of ZnO.
  • the preferred holding areas 1 , 3 , 5 , 7 and 9 have wetting properties other than the surrounding surface of the solid body, such that the liquid to be manipulated stays preferably in areas 1 , 3 , 5 , 7 and 9 .
  • the surface in the preferred holding areas is e.g. hydrophilic, as compared to the more hydrophobic surface of the remaining solid body. This can be achieved e.g. by the solid body surface in the surrounding areas being silanated or microstructured and thus becomes hydrophobic.
  • the width 2 is e.g. a few micrometers and is suited to manipulation of quantities of liquid in the picolitre to the nanolitre range.
  • Reference numerals 11 or 17 designate surface wave generation devices with beam direction 23 or 25 .
  • the illustrated embodiment concerns an interdigital transducer with electrodes 13 or 19 , with finger-like interengaging projections 15 or 21 . When an alternating filed is applied to the electrodes of the individual transducer a surface wave with a wave length corresponding to the finger distance of the electrodes is generated. The direction of dispersion is perpendicular to the interengaging fingers.
  • the transducers comprise a large number of fingers, with only a few being illustrated diagrammatically here, and not to scale.
  • Various wave types such as e.g. Rayleigh waves or shear waves can be generated by choice of crystal orientation.
  • Interdigital transducers have been created e.g. using lithographic methods and coating processes on the chip surface and are contacted via the electrodes 13 or 19 .
  • Reference numeral 26 designates the direction in which the quantity of liquid can be propelled with the help of the interdigital transducer 17 .
  • the surface of the area 5 is round and has a defined size.
  • FIG. 1 b shows a diagrammatic sectional view through the area of the solid body surface, where the preferred holding area 5 is located. A drop of liquid 27 is indicated on the solid body surface 29 .
  • the device according to the present invention of FIG. 1 is utilised as follows.
  • the “strip conductor” 1 is filled externally with the liquid to be manipulated, forming a “liquid column”. This wets the strip conductor 1 up to just in front of constriction 7 .
  • the curvature of the liquid surface is determined by the width of the “strip conductor” 1 and the volume of the quantity of liquid.
  • the quantity of liquid can be “pumped” through the constriction zone 7 all the same.
  • the required strength of the surface wave can be determined by preliminary calibration or adjusted during the experiment until the quantity of liquid moves away via the constriction zone 7 to the surface 5 . In this way a defined quantity of liquid travels from the strip conductor 1 to the defined surface 5 .
  • the required quantity of liquid is available on the surface 5 , then it can be analysed, e.g. by physical or chemical processes, or is available for reacting with another substance.
  • Whichever quantity is in each holding area 5 can be measured by measuring the attenuation of a surface wave which is sent over the area of the solid body surface, containing the surface 5 .
  • Interdigital transducers (not illustrated in the figure) can be provided for this which are opposite one another and have the surface 5 between them. If a surface wave of optionally less intensity is sent by one of these interdigital transducers in the direction of the surface 5 , then the surface wave is attenuated by the presence of the liquid. The more liquid is available, the greater the attenuation is as a rule.
  • the second opposite (also not illustrated) interdigital transducer aids in detecting the surface wave, so that the attenuation can be determined.
  • a surface wave in the direction of 25 can be sent on the quantity of liquid to the defined surface 5 .
  • the quantity of liquid is propelled via the constriction zone 9 similarly as described hereinabove for the constriction zone 7 . It reaches the strip conductor 3 through its movement in the direction of 26 . In this way a defined volume of liquid can be created.
  • this quantity of liquid is propelled from area 5 by means of the second surface wave, generated using the interdigital transducer 17 .
  • FIG. 1 accordingly allows precise definition of the smallest quantities of liquid with simultaneous planar surface of the solid body.
  • local heating e.g. with resistance heating, not show in the figures, or by means of infrared heating the surface tension of the liquid can be decreased, necessitating a lower strength of the surface wave for overcoming the constriction zone.
  • the “standard volume” of the defined surface 5 can also be adjusted within certain limits.
  • the preferred holding areas e.g. by means of a constriction zone of a “strip conductor” to a microfluid system, in which various functions of a “lab-on-a-chip” can be executed or various reactions can take place.
  • the illustrated parts of the preferred holding area can be filled by this constriction zone.
  • the constriction zone must also be sufficiently narrow for it not to be overcome by the liquid without the effect of an external force, due to its surface tension. Due to an external impulse effect, e.g. via a surface wave also, the drop of liquid can overcome this constriction zone and reach the illustrated parts of the preferred holding area.
  • a reservoir which is formed by a larger surface having the same wetting properties as the illustrated holding areas, can be situated on the other side of such a constriction zone.
  • a larger quantity of liquid can be stored thereon. Due to external impulse effect e.g. of a surface wave a quantity of liquid can be propelled out of this reservoir via the described constriction zone in the illustrated parts of the holding area.
  • the illustrated holding areas can also be filled e.g. with a pipette.
  • drops of liquid can be transported directly to specific sites on the surface and deposited there.
  • a checkerboard arrangement is shown as a special embodiment.
  • a number of defined partial areas corresponding to the area 5 of FIG. 1 a is shown, of which just a few are illustrated by way of example with 105 . These are interconnected via constriction zones 107 or 109 .
  • a “strip conductor” 100 with a greater width than the width of the constriction zones acts as supply.
  • the areas 100 , 105 , 107 , 109 again have wetting properties other than the surrounding solid body surface, similarly to the embodiment of FIG. 1.
  • groups 115 , 117 and 119 are provided with interdigital transducers which can be controlled separately.
  • the individual transducers are equipped such that the direction of dispersion is in each case along a series of constriction zones 107 or 109 .
  • this is shown on the interdigital transducer 120 by the direction of dispersion 118 .
  • the groups of interdigital transducers 119 and 117 are opposite one another.
  • Naturally another group of interdigital transducers can be provided also on the other side of the checker-board pattern opposite the group of interdigital transducers 115 .
  • a certain quantity of liquid is introduced via the “strip conductor” 100 to the defined holding area in FIG. 2 at top left.
  • Corresponding strip conductors can of course lead to other defined areas 105 also. Due to the described effect of surface tension the quantity of liquid is prevented from entering other surface areas 105 by way of the adjacent constriction zones.
  • the quantity of liquid is “pumped” away via the adjacent constriction zone to the nearest surface area 105 , as described.
  • the direction 118 sets the direction for the surface wave.
  • the drop of liquid can be transported from one area 105 to the next by corresponding switching of the interdigital transducer, until it has reached the chosen site.
  • the individual constriction zones are each emptied due to the prevalent higher internal pressure at the expense of the surfaces 105 .
  • the liquid originates e.g. from a reservoir, comprising a surface with wetting properties, such as “strip conductors”, so that the liquid preferably stays there.
  • This area may have a larger surface for storing a corresponding quantity of liquid. It is connected e.g. via the strip conductor 100 and/or a corresponding constriction zone to the system which can in turn be overcome by the liquid only by acoustic irradiation with a surface wave.
  • a partial area of defined surface 105 can be filled after the other in the direction of the surface wave 118 . If e.g. the last holding area of defined surface of a series is filled, then the process starts over from the beginning. Attenuation of the surface wave by the drop of liquid in front of it prevents drops remote from the surface wave generation device from being strongly influenced.
  • the drop of liquid in FIG. 2 can be moved in a vertical direction using the interdigital transducer of group 115 in a similar fashion.
  • a measurement can also be made as to whether the individual surfaces 105 are filled with liquid or not, as the surface wave is attenuated by the presence of the liquid.
  • the lesser amplitude is selected so that the droplets leave their respective holding area 105 not via the adjacent constriction zone.
  • Constriction zones e.g. leading to a large surface which is similarly functionalised, such as the areas 105 , 107 , 109 can of course be connected, as in FIG. 2, to the lower series of surfaces 105 .
  • the network can then be completely emptied into this large surface.
  • a “microtiter plate” for subsequent fluorescence analysis can be realised using the inventive embodiment of FIG. 2.
  • drops of liquid on various surfaces 105 are subjected to e.g. fluorescence analysis.
  • individual surfaces 105 are functionalised with a surface coating leading to a reaction. This reaction takes place locally only on this individual area and can be examined precisely.
  • a tapered interdigital transducer instead of the groups of interdigital transducers 115 , 117 , 119 , in each case a tapered interdigital transducer can be provided whose finger distance is not constant along its axis. With such tapered interdigital transducers the site of radiation can be adjusted with the frequency, since the frequency results as a quotient from the constant surface wave velocity and the wave length which corresponds to the finger distance. By setting a corresponding frequency the choice can thus be made as to which group of constriction zones situated in one line is to be addressed.
  • the individual embodiments of the invention can be combined to form a whole system.
  • the individual elements can optionally form part of a larger overall system on a single chip which has even more measuring and analysis or synthesis stations in the form of a “lab-on-the-chip”, apart from the inventive embodiments.
  • the inventive devices and methods can be used particularly advantageously for moving and positioning small quantities of liquid on such integrated systems.
  • the overall structure can be manufactured very easily using known lithographic processes and integrated on a chip with other elements which are provided e.g. for transport or analysis of small quantities of materials.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
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  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Separation Of Particles Using Liquids (AREA)
US10/450,795 2000-12-14 2001-12-12 Method and device for manipulating small quantities of liquid Abandoned US20040072366A1 (en)

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DE10062246A DE10062246C1 (de) 2000-12-14 2000-12-14 Verfahren und Vorrichtung zur Manipulation kleiner Flüssigkeitsmengen
DE10062246.1 2000-12-14
PCT/EP2001/014598 WO2002057014A1 (fr) 2000-12-14 2001-12-12 Procede et dispositif de manipulation de petites quantites de liquides

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US20020168780A1 (en) * 2001-02-09 2002-11-14 Shaorong Liu Method and apparatus for sample injection in microfabricated devices
WO2006072384A1 (fr) * 2005-01-05 2006-07-13 Advalytix Ag Procede et dispositif de dosage et de melange de petites quantites de liquide
US20060275883A1 (en) * 2003-02-27 2006-12-07 Andreas Rathgeber Method and device for blending small quantities of liquid in microcavities
US20070047388A1 (en) * 2005-08-25 2007-03-01 Rockwell Scientific Licensing, Llc Fluidic mixing structure, method for fabricating same, and mixing method
US20070062594A1 (en) * 2005-09-16 2007-03-22 Extrand Charles W Microfluidic device with anisotropic wetting surfaces
US20070065637A1 (en) * 2005-09-16 2007-03-22 Extrand Charles W Carrier with anisotropic wetting surfaces
US20070065702A1 (en) * 2005-09-16 2007-03-22 Extrand Charles W Fuel cell with anisotropic wetting surfaces
US20070264161A1 (en) * 2003-02-27 2007-11-15 Advalytix Ag Method and Device for Generating Movement in a Thin Liquid Film
US20080240995A1 (en) * 2005-12-08 2008-10-02 Olympus Corporation Reaction vessel and analyzer
US20080247264A1 (en) * 2005-09-09 2008-10-09 Siemens Aktiengesellschaft Apparatus and Method For Moving a Liquid by Means of a Piezoelectric Transducer
US20080260582A1 (en) * 2004-10-21 2008-10-23 Christoph Gauer Method for Displacing Small Amounts of Fluids in Micro Channels by Means of Acoustical Waves
US20100224274A1 (en) * 2007-07-25 2010-09-09 Canon Kabushiki Kaisha Liquid control apparatus
US20110045595A1 (en) * 2005-01-05 2011-02-24 Christoph Gauer Method and device for dosing and mixing small amounts of liquid
US20110188337A1 (en) * 2003-02-27 2011-08-04 Beckman Coulter, Inc. Method and device for generating movement in a thin liquid film

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DE10120035B4 (de) * 2001-04-24 2005-07-07 Advalytix Ag Verfahren und Vorrichtung zur Manipulation kleiner Flüssigkeitsmengen auf Oberflächen
DE10307801A1 (de) * 2003-02-24 2004-09-09 Advalytix Ag Analyseverfahren und -device zur Untersuchung von spezifischen Bindungsereignissen
JPWO2005005043A1 (ja) * 2003-07-11 2007-09-20 日本碍子株式会社 マイクロリアクター
US7048889B2 (en) * 2004-03-23 2006-05-23 Lucent Technologies Inc. Dynamically controllable biological/chemical detectors having nanostructured surfaces
DE102004037348A1 (de) * 2004-08-02 2006-03-16 Infineon Technologies Ag Fluid-Transport-Vorrichtung, Sensor-Anordnung, Fluid-Misch-Vorrichtung und Verfahren zum Herstellen einer Fluid-Transport-Vorrichtung
JP4570945B2 (ja) * 2004-12-02 2010-10-27 一般社団法人オンチップ・セロミクス・コンソーシアム 液滴操作装置及び操作方法
JP4733404B2 (ja) * 2005-02-21 2011-07-27 日本無線株式会社 弾性波センサ
DE102007021563A1 (de) 2007-05-08 2008-11-20 Universität Augsburg Vorrichtung für die Oberflächenplasmonen-Resonanzspektroskopie

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US4751530A (en) * 1986-12-19 1988-06-14 Xerox Corporation Acoustic lens arrays for ink printing
US6130098A (en) * 1995-09-15 2000-10-10 The Regents Of The University Of Michigan Moving microdroplets
US6362006B1 (en) * 2000-03-13 2002-03-26 General Electric Company Rapid parallel determination of non-volatile analytes in complex combinatorial samples
US20020031835A1 (en) * 2000-05-12 2002-03-14 University Of Delaware Laboratory-on-a-chip device using wetting forces and thermal marangoni pumping

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20020168780A1 (en) * 2001-02-09 2002-11-14 Shaorong Liu Method and apparatus for sample injection in microfabricated devices
US20070264161A1 (en) * 2003-02-27 2007-11-15 Advalytix Ag Method and Device for Generating Movement in a Thin Liquid Film
US20110188337A1 (en) * 2003-02-27 2011-08-04 Beckman Coulter, Inc. Method and device for generating movement in a thin liquid film
US20060275883A1 (en) * 2003-02-27 2006-12-07 Andreas Rathgeber Method and device for blending small quantities of liquid in microcavities
US8303778B2 (en) 2003-02-27 2012-11-06 Beckman Coulter, Inc. Method and device for generating movement in a thin liquid film
US8038337B2 (en) * 2003-02-27 2011-10-18 Beckman Coulter, Inc. Method and device for blending small quantities of liquid in microcavities
US20080260582A1 (en) * 2004-10-21 2008-10-23 Christoph Gauer Method for Displacing Small Amounts of Fluids in Micro Channels by Means of Acoustical Waves
US8062904B2 (en) 2005-01-05 2011-11-22 Beckman Coulter, Inc. Method and device for dosing and mixing small amounts of liquid
US20080186799A1 (en) * 2005-01-05 2008-08-07 Advalytix Ag Method and Device for Dosing and Mixing Small Amounts of Liquid
US20110045595A1 (en) * 2005-01-05 2011-02-24 Christoph Gauer Method and device for dosing and mixing small amounts of liquid
US8186869B2 (en) 2005-01-05 2012-05-29 Beckman Coulter, Inc. Method and device for dosing and mixing small amounts of liquid
WO2006072384A1 (fr) * 2005-01-05 2006-07-13 Advalytix Ag Procede et dispositif de dosage et de melange de petites quantites de liquide
US20070047388A1 (en) * 2005-08-25 2007-03-01 Rockwell Scientific Licensing, Llc Fluidic mixing structure, method for fabricating same, and mixing method
US20080247264A1 (en) * 2005-09-09 2008-10-09 Siemens Aktiengesellschaft Apparatus and Method For Moving a Liquid by Means of a Piezoelectric Transducer
US8240907B2 (en) 2005-09-09 2012-08-14 Siemens Aktiengesellschaft Apparatus and method for moving a liquid by means of a piezoelectric transducer
US20070065702A1 (en) * 2005-09-16 2007-03-22 Extrand Charles W Fuel cell with anisotropic wetting surfaces
US20070065637A1 (en) * 2005-09-16 2007-03-22 Extrand Charles W Carrier with anisotropic wetting surfaces
US20070062594A1 (en) * 2005-09-16 2007-03-22 Extrand Charles W Microfluidic device with anisotropic wetting surfaces
US20080240995A1 (en) * 2005-12-08 2008-10-02 Olympus Corporation Reaction vessel and analyzer
US20100224274A1 (en) * 2007-07-25 2010-09-09 Canon Kabushiki Kaisha Liquid control apparatus
US8461746B2 (en) * 2007-07-25 2013-06-11 Canon Kabushiki Kaisha Liquid control apparatus

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JP2004517335A (ja) 2004-06-10
ATE319518T1 (de) 2006-03-15
EP1345696B1 (fr) 2006-03-08
EP1345696A1 (fr) 2003-09-24
DE10062246C1 (de) 2002-05-29
DE50109179D1 (de) 2006-05-04
JP4015021B2 (ja) 2007-11-28
WO2002057014A1 (fr) 2002-07-25

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